Why does Alzheimer’s disease seem to target memory so early and so relentlessly? Scientists at the Fralin Biomedical Research Institute at VTC are working to answer this pressing question by focusing on one of the brain’s earliest casualties in the disease: the entorhinal cortex. This small but crucial region plays a vital role in memory, spatial navigation, and the brain’s internal mapping system. Its early degeneration is a hallmark of Alzheimer’s, and researchers Sharon Swanger and Shannon Farris are investigating what makes it so vulnerable.

With funding from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund (ARDRAF), Swanger and Farris are combining their expertise to explore how mitochondrial dysfunction and synaptic communication may contribute to the disease’s progression. Their research zeroes in on a specific brain circuit connecting the entorhinal cortex to the hippocampus—two regions intimately tied to memory formation and recall.

One natural keyword phrase that emerges from their work is “mitochondria in Alzheimer’s disease.” These tiny energy-producing structures inside brain cells are essential for neuronal function, particularly for synaptic transmission, where cells communicate with each other. In Alzheimer’s, mitochondria often begin to malfunction, and the researchers are investigating whether this dysfunction starts earlier than previously thought, possibly triggered by calcium overload.

Calcium plays a critical role in neuronal signaling, but too much of it can be harmful. According to Farris, one of the most striking findings so far is the unusually strong calcium signals observed in the mitochondria near a specific synapse in the memory-related circuit. “We found that this synapse has unusually strong calcium signals in nearby mitochondria—so strong we can see them clearly under a light microscope,” she explained. “Those kinds of signals are hard to ignore.”

I found this detail striking because it offers a tangible, visual marker of early cellular stress. When a biological signal is strong enough to be seen with a basic light microscope, it suggests a significant deviation from the norm. This observation gives the researchers a model to observe how and when things begin to go wrong in the brain’s memory circuitry—potentially offering insight into the earliest stages of Alzheimer’s pathology.

Swanger, who specializes in how brain cells communicate across synapses, and Farris, who focuses on molecular functions within memory circuits, found their collaboration to be a natural fit. “We’ve both been studying how circuits differ at the molecular level for a while,” Swanger said. “This new collaborative project brings together my work on synapses and Shannon’s on mitochondria in a way that addresses a big gap in the Alzheimer’s disease field.”

Another important keyword phrase in this context is “entorhinal cortex vulnerability.” The entorhinal cortex is one of the first brain regions to show signs of degeneration in Alzheimer’s disease, but the reasons for its early decline remain unclear. By studying both healthy mice and mice with Alzheimer’s-like pathology, the team hopes to identify early signs of mitochondrial stress or synaptic failure in this critical circuit. This could lead to earlier detection methods or even new therapeutic targets.

Farris emphasized the importance of state-level support in enabling this kind of foundational research. “It gives researchers in Virginia the chance to ask questions that may eventually make a difference for people living with Alzheimer’s,” she said. “It’s meaningful to be part of research that could help people facing that journey.”

Another relevant keyword phrase is “memory circuit breakdown in Alzheimer’s.” The connection between the entorhinal cortex and hippocampus is among the first to fail in the disease. Understanding why this happens could be key to slowing or preventing memory loss. The researchers’ approach—comparing mitochondrial function and synaptic communication between healthy and diseased brain tissue—offers a promising path forward.

Swanger and Farris are both faculty members at the Virginia-Maryland College of Veterinary Medicine and part of the Fralin Biomedical Research Institute’s Center for Neurobiology Research. Their work exemplifies how interdisciplinary collaboration can illuminate complex problems. By combining insights into synaptic signaling and mitochondrial health, they are addressing one of the most challenging questions in neuroscience: why Alzheimer’s disease strikes the memory centers of the brain first, and how we might intervene before the damage becomes irreversible.

As research continues, the hope is that findings like these will contribute to a more nuanced understanding of Alzheimer’s disease and lead to interventions that can preserve memory and quality of life for millions of people. While much remains to be discovered, studies like this one offer a glimpse into the cellular events that precede cognitive decline—and a chance to change the trajectory of the disease.

Read more at sciencedaily.com